An endogenous pentapeptide acting as a sodium channel blocker in inflammatory autoimmune disorders o

Abstract

Reversible blockade of sodium channels by endogenous substances has been claimed to account for the fast exacerbations and relapses commonly seen in demyelinating autoimmune diseases2,3,4. Evidence has been provided that in the cerebrospinal fluid of patients with multiple sclerosis5 or Guillain-Barré syndrome6, a sodium-channel-blocking factor exists that has properties of local anesthetic agents7,8. This factor could contribute to the nerve conduction block and paresis seen in these disorders9,10,11. We describe here a previously unknown endogenous substance in human cerebrospinal fluid with distinct channel-blocking properties even at very low (0.00001 M) concentrations. The pentapeptide with the sequence Gln-Tyr-Asn-Ala-Asp exerted its blocking action by shifting the steady-state inactivation curve of the sodium channels to more-negative potentials, as most local anesthetics do. In the cerebrospinal fluid of healthy individuals, its concentration was about 3 μM, whereas in patients with multiple sclerosis and Guillain-Barré syndrome, it increased 300–1,400%. At these concentrations, the peptide's blocking efficacy was higher than that of 50 μM lidocaine. At a concentration of 10 μM, lidocaine is able to ‘unmask’ subclinical lesions in multiple sclerosis12; thus, the endogenous pentapeptide may well contribute to the fast changes of symptoms. Furthermore, it may become valuable as a marker of disease activity.

Cite this article

Brinkmeier, H., Aulkemeyer, P., Wollinsky, K. et al. An endogenous pentapeptide acting as a sodium channel blocker in inflammatory autoimmune disorders of the central nervous system. Nat Med 6, 808–811 (2000). https://doi.org/10.1038/77543

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